Zicam Nasal Gel: Questions about Efficacy, Risk of Use, and Timing of the Warning

Armand Rossetti — Fri, 19 Jun 2009 17:14:06 GMT

The three Zicam products included in the recent FDA warning letter that Matrixx received in June 2009 are:

Zicam Cold Remedy Nasal Gel (NDC 62750-003-10)
Zicam Cold Remedy Swabs (NDC 62750-003-20)
Zicam Cold Remedy Swabs, Kids Size (NDC 62750-003-21) (discontinued)

Zicam Cold Remedy Nasal Swabs and Zicam Cold Remedy Nasal Gel were both introduced in 1999 and each contain the active ingredient, zinc gluconate (10% ).

There are many questions to consider when analyzing the reason for, and the timing of the FDA’s warning. However, it might be best to take a brief look at whether zinc products such as Zicam Cold Remedy actually work as homeopathic remedies.

The trademark, Zicam, is taken from “Z” for zinc and I-CAM, a type of receptor site found on epithelial cells and in viruses. Purportedly, Zn2+ ions complex with intercellular adhesion molecular receptor sites on rhinovirus surfaces, and prevent cold viruses from binding to human cells. In other words, zinc allegedly prevents cold viruses from gaining entry to human cells and causing cold symptoms.

It all looks pretty simple and straight forward. However over the years, Zinc’s efficacy as a virus blocker has been the subject of notable controversy.

In 2000, Michael Hirt’s group published a study in the Ear, Nose & Throat Journal that suggested that zinc lozenges shortened the number of days from onset to the complete resolution of common colds. Hirt found that zinc lozenges reduced the duration of symptoms by 75%, which was consistent with the 85% figure that Hensley (in an unpublished zinc nasal gel study) had reported. However, another investigator found otherwise.

In 2001, Ronald Turner found that there was no significant effect, i.e., no difference in common cold duration between active zinc treated and placebo treated subjects. Turner noted that the infection rate in challenge volunteers was 93% while it was 90% the placebo volunteers. During the study, Turner measured signs and symptoms such as rhinovirus severity, nasal obstruction, and headache. In 2002 Samuel Yiu corresponded with Turner. While Yiu supported Turner’s challenge model, he found fault with the sample population number and protocol of the study. In his correspondence, Yiu also suggested that further evaluation was necessary in order to draw any conclusion regarding efficacy.

In 2004, Hulisz published an overview concerning zinc’s efficacy against the common cold Hulisz found that zinc attached to “I-CAM receptor sites found on retroviruses and on nasal epithelial cells. However, Hulisz also determined that there was a 24-hour window, beginning onset, for the most effective treatment to occur. A question might arise whether the average consumer can accurately determine when that window opens and when it closes.

Is nasal zinc treatment worth the risk? We have seen some evidence (above) that zinc may or may not work under certain circumstances. However, what is the risk of using nasal zinc products?

In 1938, amidst a polio epidemic that prompted physicians to arrive at ways to prevent the poliovirus from spreading, Smith submitted a study to the Canadian Medical Association Journal that addressed epithelial treatment with 1% zinc sulphate. Although zinc sulphate is not exactly the same as zinc gluconate, it seems evident that both are severe irritants at higher concentrations.

In his basic science study, Smith found evidence that zinc sulfate at 1% destroyed the three types of cells in the olfactory sensory epithelium that gives humans the ability to smell known in scientific circles as “anosmia.” More importantly, those sensory cells disappeared forever because they cannot regenerate. Instead, regular non-sensory epithelial cells replaced those sensory cells.

Given all of the above, it is not unreasonable to question whether the risk of using nasal zinc treatment might outweigh the benefit of receiving such treatment. After all, the FDA’s concerns about reported adverse events of anosmia were underscored by published scientific literature that provided evidence, such as the 1938 Smith study, showing a connection between intranasal zinc and anosmia.

Next we should question when the risk of using Zicam gel nasal spray became obvious.

As early as October 2003, Zicam, LLC and parent, Matrixx Initiatives, Inc. became defendants in a lawsuit that alleged that the plaintiff had lost his sense of smell after only a single treatment with Zicam. In fact by 2004, large numbers of similar complaints prompted the FDA to inquire about Zicam’s safety.

As time progressed, claimants continued filing complaints, alleging that treatment with Zicam nasal spray (a gel) had caused loss of smell. It is interesting to know that that FDA was not regulating homeopathic zinc preparations such as the Zicam Cold Remedy.

Later on in February 2006, Matrixx settled 340 anosmia-related Zicam lawsuits. Then, as previously mentioned, more than three years later on June 16, 2009, the FDA issued a warning letter to Matrixx . The warning letter notified Matrixx that it had crossed the line when making efficacy claims for its self-declared “homeopathic,” nasal zinc products. Therefore, Matrixx could no longer qualify those products as being homeopathic preparations. According to the FDA, Matrixx had taken a step further and was actually marketing new drugs intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease, all without FDA approval. As required before marketing Zicam Cold Remedy Nasal Gel and Swabs, Matrix had not submitted a new drug application (NDA), and it had not participated in the FDA approval process. As a result, the FDA suggested that Matrixx promptly remove Zicam Cold Remedy nasal products from store shelves.

To this day, however, Matrixx maintains its original position that Zicam nasal preparations are scientifically proven to be safe and efficacious, and that they do not cause anosmia. Yet, only three days after receiving the FDA warning, Matrixx issued a message, suggesting, among other actions, that consumers discard any previously purchased Zicam Cold Remedy Nasal Gel or Zicam Cold Remedy Gel Swabs.

These precautions are all “good and well,” but at what point should consumers have received a formal manufacturer’s warning concerning the possible danger associated with nasal application of Zicam Cold Remedy? Would the right time have been in 1999, when Matrixx introduced Zicam nasal zinc products? How about in 2003, when plaintiffs allegedly suffering with anosmia filed 340 lawsuits? Should Matrixx have issued a voluntary preliminary warning in 2004, when the FDA began investigating complaints; or should Matrixx have then instructed consumers concerning proper application and use?

It seems plausible that Matrixx might have issued a voluntary warning in 2006, when it settled 340 Zicam lawsuits for 12 million dollars. In fact, George Eby submitted an article to Alternative Therapies in 2006 that contained the following statement:

“We contend that it is unethical to introduce any potentially permanent anosmia-inducing agent such as zinc or other heavy metals into the interior of the nose in a manner that could result in contact with the olfactory region to treat a temporary discomfort such as a common cold or allergy. We found no reason to recommend intranasal zinc gluconate or zinc orotate lozenges in treating common colds. (Altern Ther Health Med. 2006;12(1):34-38.) [Emphasis added].”

In 2006, additional information about the danger in using Zicam gel continued emerging. For example, the Denver Naturopathic Clinic issued a Zicam caution in 2006; the clinic provided a well reasoned opinion why Zicam was not homeopathic, and at least one clinic had raised a question about Zicam’s efficacy.

Maybe after receiving 800 aftermarket consumer complaints involving anosmia, the FDA might have suggested that Matrixx issue a warning in 2007 or 2008. What standard would be necessary to analyze whether a warning was warranted?

Perhaps Justice Royal in McClain v. Metabolife, 401 F.3d 1233 (11^th Cir. 2005) mentioned the difference between assessing consumer risk (a lower, more encompassing standard) and determining scientifically based causation (a more demanding and higher standard):

“The FDA will remove drugs from the marketplace upon a lesser showing of harm to the public than the preponderance-of-the-evidence or the more-like-than-not standard used to assess tort liability. The methodology employed by a government agency results from the preventive perspective that the agencies adopt in order to reduce public exposure to harmful substances....”

Therefore in Matrixx' case, it should be reasonable to conclude that whenever that lesser showing of harm occurred, and I suspect that it occurred at least a few years before 2009, Matrixx should have issued a voluntarily warning, or the FDA should have suggested that it do so.

Originally posted at InjuryBoard by Armand Rossetti

West Palm Beach Personal Injury Lawyer - Zicam Cold Remedy

Zicam Nasal Gel: Questions about Efficacy, Risk of Use, and Timing of the Warning